The pathogenesis of degenerative diseases of aging involves the loss of important functional cell types. Apoptosis is a form of programmed cell death that is responsible for the elimination of many cell types during development. The goal of this project is to determine the importance of apoptosis in the biology of the chondrocyte. One class of retinoic acid receptors, the RARa family, plays a major role in mediating the apoptotic response in chondrocytes. Recent efforts are directed towards optimizing the in situ detection of fragmented DNA in cartilaginous tissue. Preliminary results with articular cartilage samples from rats and monkeys suggest that a small number of cells deep in the articular cartilage of older animals contain fragmented DNA and are undergoing apoptosis.